Aminocarbonylation Reaction Research Articles

N,N-Dimethylformamide solvothermal strategy: From fabrication of palladium nanoparticles supported on reduced graphene oxide nanosheets to their application in catalytic aminocarbonylation reactions

A facile N,N-dimethylformamide (DMF) solvothermal strategy has been developed to fabricate palladium nanoparticles supported on reduced graphene oxide nanosheets (SRGO-Pd), which efficiently catalyze the aminocarbonylation of aryl halides. The palladium nanoparticles were uniformly anchored on the reduced graphene oxide nanosheets by a one-step DMF solvothermal approach. During the process, the palladium particles on the reduced graphene oxide nanosheets were tuned by the solvothermal temperature. DMF did not only play the role of the reductant for graphite oxide and Pd2+, but also restrained the aggregation of the graphene sheets and stabilized the palladium nanoparticles. Under DMF solvothermal conditions, SRGO-Pd catalysts demonstrated an excellent catalytic activity and good recyclability for the aminocarbonylation reaction of aryl halides without using carbon monoxide and any other additive. The SRGO-Pd catalyst could be recycled at least eight times with sustained activity. Such a strategy represents a promising route for applications ranging from the fabrication of graphene-supported materials to the use as catalysts.

Efficient Fluoride-Catalyzed Conversion of CO2 to CO at Room Temperature

A protocol for the efficient and selective reduction of carbon dioxide to carbon monoxide has been developed. Remarkably, this oxygen abstraction step can be performed with only the presence of catalytic cesium fluoride and a stoichiometric amount of a disilane in DMSO at room temperature. Rapid reduction of CO2 to CO could be achieved in only 2 h, which was observed by pressure measurements. To quantify the amount of CO produced, the reduction was coupled to an aminocarbonylation reaction using the two-chamber system, COware. The reduction was not limited to a specific disilane, since (Ph2MeSi)2 as well as (PhMe2Si)2 and (Me3Si)3SiH exhibited similar reactivity. Moreover, at a slightly elevated temperature, other fluoride salts were able to efficiently catalyze the CO2 to CO reduction. Employing a nonhygroscopic fluoride source, KHF2, omitted the need for an inert atmosphere. Substituting the disilane with silylborane, (pinacolato)BSiMe2Ph, maintained the high activity of the system, whereas the structurally related bis(pinacolato)diboron could not be activated with this fluoride methodology. Furthermore, this chemistry could be adapted to (13)C-isotope labeling of six pharmaceutically relevant compounds starting from Ba(13)CO3 in a newly developed three-chamber system.

Palladium(II) chalcogenolate complexes as catalysts for C[sbnd]C cross-coupling and carbonylative Suzuki coupling reactions

The catalytic activity of palladium chalcogenolate complexes, [PdCl(ECH2CH2NMe2)]3 (E=S or Se), [PdCl(ECH2CH2CH2NMe2)]2 and [PdCl(SeCH2CH2NMe2)(PPh3)] has been investigated in carbonylative Suzuki coupling reactions. The phosphine complex has also been used as a catalyst in CC cross coupling reactions involving an aryl halide and either triaryl bismuth or aryl boronic acid (Suzuki coupling). The catalytic system was also explored for other carbonylation reactions including carbonylative Sonogashira coupling and amino carbonylation reaction. The phosphine complex showed better activity in carbonylative Suzuki coupling reactions than dimeric and trimeric complexes. All the complexes showed comparable activity in Suzuki coupling reactions.

AMINOCARBONYLATION REACTION USING PALLADIUM COMPLEXES CONTAINING PHOSPHORUS-NITROGEN LIGANDS AS CATALYSTS

The catalytic activities of palladium complexes containing phosphorus-nitrogen ligands is reported. The catalysts studied showed high activities in the aminocarbonylation of aryl iodides. The palladium complexes reported activities between 100% and 58% in the aminocarbonylation reaction. The reactions are very selective for the double carbonylative amination of aryl halides. The major product is N,N-diethyl-α-oxo benzeneacetamide (96/4). The reaction was made under mild conditions of temperature and carbon monoxide pressure.

ChemInform Abstract: Palladium‐Catalyzed Oxidative Aminocarbonylation: A New Entry to Amides via C—H Activation.

A novel palladium-catalyzed oxidative aminocarbonylation reaction via C(sp3)–H activation was established, which provides a convenient and general method for the construction of arylacetamides via the carbonylation reaction of alkyl aromatics and amines. By using this protocol, the marketed drug ibuprofen could be easily obtained.

Synthesis and Evaluation of a 18F-Labeled Diarylpyrazole Glycoconjugate for the Imaging of NTS1-Positive Tumors

Aiming to image NTS1 overexpressing tumors, the diarylpyrazole glycoconjugate 8, derived from the potent NTS1 antagonist SR142948A, was synthesized taking advantage of the palladium-catalyzed aminocarbonylation reaction. The glycoconjugate 8 displayed excellent affinity and selectivity toward NTS1. Radiosynthesis proceeded straightforwardly, obtaining [(18)F]8 with excellent stability and highly beneficial biodistribution in vivo as demonstrated by PET imaging in HT29 tumor-bearing nude mice. Thus, the tracer [(18)F]8 represents a highly promising candidate for PET imaging of NTS1-positive tumors.

Synthesis of novel 13α-18-nor-16-carboxamido steroids via a palladium-catalyzed aminocarbonylation reaction

13α-18-nor-16-Carboxamido steroids were synthesized via a palladium-catalyzed aminocarbonylation reaction of the corresponding iodoalkenes. The starting material was an unnatural 13α-16-keto steroid, obtained by a Wagner–Meerwein rearrangement of a 16α,17α-epoxide in the presence of [BMIM][BF4]. The 13α-16-keto steroid was converted to a mixture of 16-iodo-16-ene and 16-iodo-15-ene derivatives in two steps by Barton’s methodology. Aminocarbonylation of the steroidal alkenyl iodides was carried out using different primary and secondary amines as nucleophiles. The products, 16-carboxamido-16-ene and 16-carboxamido-15-ene derivatives, were obtained in good yields and were characterized by 1H and 13C NMR, IR and MS.The reduction of the above two unsaturated carboxamides resulted in the same product, 17α-methyl-16α-carboxamido-androstane.

Efficient Synthesis of Heterocyclic Neurotensin Receptor Ligands by Microwave-Assisted Aminocarbonylation

Marking the heterocyclic neurotensin receptor antagonist SR142948A as a lead compound, the development of an efficient and a practical synthetic route to heterocyclic aryl carboxamides is reported. Thus, a highly efficient and flexible access to these carboxamides was elaborated by taking advantage of microwave-assisted aminocarbonylation reaction mediated by Mo(CO)6, Herrmann’s palladacycle, [(t-Bu)3PH]BF4, and DBU.

Palladium-Catalyzed Oxidative Aminocarbonylation: A New Entry to Amides via C–H Activation

A novel palladium-catalyzed oxidative aminocarbonylation reaction via C(sp(3))-H activation was established, which provides a convenient and general method for the construction of arylacetamides via the carbonylation reaction of alkyl aromatics and amines. By using this protocol, the marketed drug ibuprofen could be easily obtained.

Sequential one-pot synthesis of benzoxazoles from aryl bromides: successive palladium- and copper-catalyzed reactions

A convenient one-pot process has been developed for the synthesis of benzoxazoles. Starting from aryl bromides and 1,2-dibromobenzenes palladium-catalyzed aminocarbonylation and subsequent copper-catalyzed coupling reaction gave a variety of substituted benzoxazoles in moderate to good yields.

Palladium-Catalyzed Synthesis of Benzimidazoles and Quinazolinones from Common Precursors

N-(o-Halophenyl)imidoyl chlorides and the corresponding imidates are easily prepared and can be utilized as complementary precursors for the synthesis of important heterocycles. The synthesis of N-substituted benzimidazoles was possible from the palladium-catalyzed reaction of both classes of substrate with a variety of N-nucleophiles. The use of the imidate precursor for the synthesis of N-substituted quinazolinones by incorporation of a palladium-catalyzed aminocarbonylation reaction has also been demonstrated. Both processes tolerate a wide range of functional groups.

Synthesis of new steroid-β-lactam hybrids via palladium-catalyzed aminocarbonylation

Steroid-β-lactam and steroid-β-lactam-ferrocene conjugates were synthesized via palladium-catalyzed carbonylation of steroidal 17-iodo-16-enes in the presence of 3-amino-azetidin-2-ones. β-Lactam derivatives have been used for the first time as nucleophiles in the aminocarbonylation reaction. The products were obtained in good yields and were characterized by 1H and 13C NMR, IR and HRMS.

A DFT study of the mechanism of palladium-catalyzed alkoxycarbonylation and aminocarbonylation of alkynes: Hydride versus amine pathways

A DFT study on the palladium-bisphosphine catalyzed alkoxycarbonylation and aminocarbonylation of alkyne (propyne) is reported. The theoretical study explores the feasibility and the regioselectivity control of two independent mechanisms: the first is based on the active intermediate [Pd(II)(P 2)(H)] + (where P 2 = PH 2CH 2CH 2CH 2CH 2PH 2) for the alkoxycarbonylation reaction, and the second is based on the active species [Pd(II)(P 2)(NR 2)] + for the aminocarbonylation reaction. The study explains the role of solvent in increasing the yield and in controlling the selectivity of reaction to produce selectively the trans isomer in the alkoxycarbonylation reaction (hydride cycle) and the gem isomer in the aminocarbonylation reaction (amine cycle). In hydride cycle, the regioselectivity is mainly determined by the stability of the complex [Pd(II)(P 2)(COC 3H 5)(CH 3CN)] +; however, for the amine cycle, the regioselectivity is determined by the stability of the complex [Pd(II)(P 2)(C 3H 5CON(CH 3) 2)] +. The calculations reveal that ligand simplification is not valid in addressing the regioselectivity behavior of alkoxycarbonylation and aminocarbonylation reactions. The kinetic data for the formation of the two key complexes show no difference between the gem and trans isomers which predict the regioselectivity to be a thermodynamically controlled process.

Stabilized well-dispersed Pd(0) nanoparticles for aminocarbonylation of aryl halides

Well-dispersed palladium (0) nanoparticles stabilized with phosphonium based ionic liquid were synthesized conveniently and fully characterized. A catalyst system comprising of the Pd(0) nanoparticles and a base was found to be recyclable and efficient for the aminocarbonylation reaction of aryl iodide in ionic liquid media. In the presence of potassium tert-butyloxide, for the relatively stable aryl chloride and bromide substrates, medium activities were achieved for the catalyst. The catalyst composites can be recycled at least five times with sustained activity.

Systematic investigation on the synthesis of androstane-based 3-, 11- and 17-carboxamides via palladium-catalyzed aminocarbonylation

3,17-Dicarboxamido-androst-3,5,16-triene, 3-carboxamido-androst-3,5-dien-17-one, 17-carboxamido-androst-4,16-dien-3-one and 11-carboxamido-androst-5,9(11)-dien-3,17-dione derivatives were synthesized in homogeneous carbonylation reactions from the corresponding 3,17-diiodo-androst-3,5,16-triene, 3-iodo-androst-3,5-diene-17-ethylene ketal, 17-iodo-androst-5,16-dien-3-ethylene ketal, 11-iodo-androst-5,9(11)-diene-3,17-bis(ethylene ketal) derivatives, respectively. A highly chemoselective palladium-catalyzed aminocarbonylation of the corresponding iodo-alkene, carried out under mild reaction conditions, can be considered as the key-step for the introduction of the carboxamide functionalities. The synthesis of the iodo-alkene substrate is based on the transformation of the corresponding keto derivative to hydrazone, which was treated with iodine in the presence of a base (1,1,3,3-tetramethyl guanidine). The aminocarbonylation reaction is highly tolerant towards the N-nucleophiles, i.e. various primary and secondary amines including amino acid methyl esters can also be used.

A Microfluidic Approach to the Rapid Screening of Palladium‐Catalysed Aminocarbonylation Reactions

AbstractThe evaluation and selection of the most appropriate catalyst for a chemical transformation is an important process in many areas of synthetic chemistry. Conventional catalyst screening involving batch reactor systems can be both time‐consuming and expensive, resulting in a large number of individual chemical reactions. Continuous flow microfluidic reactors are increasingly viewed as a powerful alternative format for reacting and processing larger numbers of small‐scale reactions in a rapid, more controlled and safer fashion. In this study we demonstrate the use of a planar glass microfluidic reactor for performing the three‐component palladium‐catalysed aminocarbonylation reaction of iodobenzene, benzylamine and carbon monoxide to form N‐benzylbenzamide, and screen a series of palladium catalysts over a range of temperatures. N‐Benzylbenzamide product yields for this reaction were found to be highly dependent on the nature of the catalyst and reaction temperature. The majority of catalysts gave good to high yields under typical flow conditions at high temperatures (150 °C), however the palladium(II) chloride‐Xantphos complex [PdCl2(Xantphos)] proved to be far superior as a catalyst at lower temperatures (75–120 °C). The utilised method was found to be an efficent and reliable way for screening a large number of palladium‐catalysed carbonylation reactions and may prove useful in screening other gas/liquid phase reactions.

Aminocarbonylations of alkenyl phosphates, chlorides, bromides, and triflates with Mo(CO) 6 as a solid CO source

Palladium-catalyzed aminocarbonylations of alkenyl chlorides, bromides, and triflates were investigated using Mo(CO) 6 as a solid carbon monoxide source. The reactions afforded moderate to good yields producing a wide variety of acrylamides after 20 min of microwave irradiation. In addition, the aminocarbonylation reaction was, for the first time, expanded to include alkenyl phosphates as starting materials.

Palladium‐Catalysed Multicomponent Aminocarbonylation of Aryl or Heteroaryl Halides with [Mo(CO)6] and Aryl‐ or ­Heteroarylamines Using Conventional Heating

AbstractDi(hetero)arylamides have been synthesized in short reaction times by palladium‐catalysed multicomponent aminocarbonylation of either electron‐deficient or electron‐rich heteroaryl halides and p‐iodoanisole with several arylamines bearing either electron‐donating or ‐withdrawing groups and aminopyridines using [Mo(CO)6] as a solid CO source and conventional heating. Starting from heteroaryl bromides, a palladacycle with tBu3PHBF4 as ligand is required together with DBU as a base in dioxane and a temperature of 125 °C. From (hetero)aryl iodides, Pd(OAc)2 without a ligand and DBU were used in dioxane at 110 °C. Under the latter conditions we were able to apply this reaction to deactivated aminopyridines to obtain the corresponding di(hetero)arylamides. We have demonstrated that these reactions can be performed under conventional heating (110–125 °C) to yield the corresponding di(hetero)arylamides in moderate‐to‐high yields in short reaction times (from 1–3 h) with no need for MW irradiation. A N‐substituted isoindoline‐1,3‐dione from 2‐iodobenzoic acid or methyl 2‐iodobenzoate and p‐anisidine through a one‐step carbonylative cyclization reaction was also obtained. Thus, we have extended the scope of thispalladium‐catalysed aminocarbonylation reaction with [Mo(CO)6] to several (hetero)aryl substrates using conventional heating. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

High-yielding synthesis of 2-arylacrylamides via homogeneous catalytic aminocarbonylation of α-iodostyrene and α,α′-diiodo-1,4-divinylbenzene

Highly reactive iodoalkenes (α-iodostyrene and α,α′-diiodo-1,4-divinylbenzene) were prepared and used as substrates in palladium-catalysed aminocarbonylation reaction. Regardless of the type of amine nucleophile the corresponding N-substituted phenylacrylamides have been formed chemoselectively in nearly quantitative yields. High isolated yields (up to 83%) have been achieved both with unfunctionalised simple amines and amino acid methyl esters under mild reaction conditions.

Aminocarbonylation of Aryl Halides Using a Nickel Phosphite Catalytic System

The nickel and phosphite catalytic system with sodium methoxide enables a very efficient aminocarbonylation reaction to be performed between aryl iodides or bromides and N,N-dimethylformamide (DMF). Phosphite ligand 1, which is very stable to air and moisture and, furthermore, inexpensive, afforded the highest reaction yield.